Isoniazid preventive therapy and risk for resistant tuberculosis

Abstract

In the context of tuberculosis (TB) resurgence, isoniazid preventive therapy (IPT) is increasingly promoted, but concerns about the risk for development of isoniazid-resistant tuberculosis may hinder its widespread implementation. We conducted a systematic review of data published since 1951 to assess the effect of primary IPT on the risk for isoniazid-resistant TB. Different definitions of isoniazid resistance were used, which affected summary effect estimates; we report the most consistent results. When all 13 studies (N = 18,095 persons in isoniazid groups and N = 17,985 persons in control groups) were combined, the summary relative risk for resistance was 1.45 (95% confidence interval 0.85-2.47). Results were similar when studies of HIV-uninfected and HIV-infected persons were considered separately. Analyses were limited by small numbers and incomplete testing of isolates, but findings do not exclude an increased risk for isoniazid-resistant TB after IPT. The diagnosis of active TB should be excluded before IPT. Continued surveillance for isoniazid resistance is essential.

Figure 1

Relative risk (RR) for isoniazid resistance associated with isoniazid preventive therapy in 13 studies. A) Using definition (a) of resistance for the Greenland study (20). B) Using definition (b) of resistance for the Greenland study. *Excluding the 4 studies with no resistant cases in 1 or both of the 2 groups. The squares and horizontal lines represent the relative risk (RR) and 95% confidence intervals (CIs) for each study. The diamonds represent the summary RR and 95% CIs.

Figure 2

Funnel plots to detect publication bias for studies reporting the effect of isoniazid preventive therapy on risk for isoniazid-resistant tuberculosis. The log relative risk (RR) for each study is plotted against the standard error of the natural log (ln) of the RR. The horizontal line indicates the (log) summary RR, and guidelines to assist in visualizing the funnel are plotted at the 95% pseudoconfidence limits about the summary RR estimate. A) Using definition (a) of resistance for the Greenland study (20); B) using definition (b) of resistance for the Greenland study.